Chapter 43: The Immune System

Essential Knowledge2.d.2 - Homeostatic mechanisms reflect both

common ancestry and divergence due to adaptation to different environments (43.3).

2.d.3 – Biological systems are affected by disruptions to their dynamic homeostasis (43.2-43.4).

2.d.4 – Plants and animals have a variety of chemical defenses against infections that affect dynamic homeostasis (43.1-43.4).

3.d.2 Cells communicate with each other through direct contact with other cells or from a distance via chemical signaling (43.2).

Focus TopicsImmunological responses to pathogens,

toxins, and allergensVertebrate immune systems have nonspecific

and nonheritable defense mechanisms against pathogens

The mammalian immune system includes two types of specific responses: cell mediated and humoral

In the cell-mediated response, cytotoxic T cells, a type of lymphocytic white blood cell, “target” intracellular pathogens when antigens are displayed on the outside of the cells.

Focus TopicsIn the humoral response, B cells, a type

of lymphocytic white blood cell, produce antibodies against specific antigens.

Antigens are recognized by antibodies to the antigen.

Antibodies are proteins produced by B cells, and each antibody is specific to a particular antigen.

A second exposure to an antigen results in a more rapid and enhanced immune response.

Introduction to ImmunityDefense systemProtects from bacteria, viruses, other

pathogens, early-stage cancer cellsThree types of immunity:

1. Innate: nonspecific defense mechanisms external physical barriers of skin mucous membranes

internal defenses of chemicals and phagocytic cells

Ex: gastric juices, histamines, inflammatory response

Introduction to ImmunityThree types of immunity:

2. Acquired: adaptive immunity, line of defense in which lymphocytes react specifically to threat, two types Humoral – antibodies produced by cells

mark microbes for destruction, involves B cells

Cell-mediated – cytotoxic lymphocytes destroy infected body cells, cancer cells and foreign tissue, involves helper T cells

3. Passive: acquired temporarily◦ Ex: through breast-feeding

http://en.wikipedia.org/wiki/Image:Immunity.png

Organs/Tissues/Glands involved:◦ Bone/bone marrow◦ Spleen◦ Stomach/

Intestines◦ Skin◦ Lungs◦ Lymph nodes

Introduction to Immunity

Leukocytes are the cells which are the bulk of your immune system.◦Produced or stored in:

Thymus, spleen, and bone marrow (called the lymphoid organs)

There are also clumps of lymphoid tissue throughout the body (primarily as lymph nodes) that hold leukocytes

Introduction to Immunity

The two basic types of leukocytes are:◦Phagocytes, cells that chew up

invading organisms Ex: neutrophils

◦Lymphocytes, cells that allow the body to remember and recognize previous invaders and help the body destroy them Ex: B and T cells

The leukocytes circulate through the body between the organs and nodes via lymphatic vessels and blood vessels.

In this way, the immune system works in a coordinated manner to monitor the body for germs or substances that might cause problems.

Introduction to Immunity

Innate ImmunityExternal defenses

◦Skin – secretions lower pH (discourage microbial attack)

◦Mucous membranes (line digestive, respiratory, genitourinary tracts) Gastric juice – lowers pH to acidic Epilethial lining of respiratory – traps

microbes

◦Lysozyme – enzyme that attacks bacterial cell walls Present in tears, saliva, and mucus

◦Serve as physical barriers to microbes

Innate ImmunityInternal defenses

◦Systemic response may include: Increase in number of circulating WBCs Fever

Triggered by toxins produced by pathogen or chemicals released by immune system

Stimulates phagocytosis and thus tissue repair and immune response

Inflammation Redness, swelling, heat Occurs when damaged mast cells (in connective

tissue) release histamine Histamine: triggers dilation and leakiness of

blood vessels

Innate ImmunityInternal defenses

◦Relies upon phagocytosis by special WBCs (phagocytes) These cells release antimicrobial proteins to

help initiate an inflammation response Rely upon cell surface rectors to bind to microbial

surface receptors Then, engulfs microbe and kill them using lysosome

toxins Neutrophils: most numerous phagocytic

WBCs Eosinophils: WBCs that attack multicellular

parasites Dendritic cells: stimulate acquired

immunity

Innate ImmunityInternal defenses

◦Natural killer (NK) cells: nonphagocytic cells that also participate in innate defenses Recognize general features of viral-infected or

cancer cells Attaches to them and triggers apoptosis

◦Complement system: 30 proteins that can lyse microbes, trigger inflammation or assist in acquired immunity

◦Interferons: stimulate neighboring cell to produce anti-viral reproduction substances

Acquired ImmunityIntroduction

◦First visit: Immune System Preview◦Key cells: lymphocytes (WBCs)◦Activated by contact with microbes OR

by cytokines (proteins secreted by macrophages)

◦Recognizes antigens (foreign molecules) Most are large proteins or polysaccharides Often protrude from surface of microbe Epitope: region of antigen to which

lymphocyte attaches

Acquired ImmunityAntigen Recognition

◦Performed by B and T cells B lymphocytes (B cells) and T

lymphocytes (T cells) circulate in blood and lymph

Found in spleen and lymph nodes Recognized by antibodies to the

particular antigen Both contain membrane-bound antigen

receptors which allows them to recognize specific epitopes (where they will bind)

Acquired ImmunityAntigen Recognition

◦B cell receptor Y-shaped Consists of 4 polypeptide chains (two

light chains and two heavy chains)

◦T cell receptor One alpha chain and one beta chain Recognize special cell-surface proteins

made by MHC (major histocompatibility complex – a family of genes)

Acquired ImmunityPrimary immune response

◦Begins this response upon first exposure to an antigen (foreign molecule)

◦Requires about 10-17 days to yield maximum response via T and B-cells

◦ Immunological memory: secondary immune response that provides long-term protection against a previously encountered pathogen “To avoid illness, expose yourself to germs,

enabling your immune system to develop antibodies. I don’t know why everyone doesn’t do this. Maybe they have something against living forever.” ~Dwight Schrute

Acquired ImmunityTwo types:

◦Humoral immune response Involves B cell activation and production of

antibodies Antibodies then circulate in blood and lymph Provide defense against pathogens and toxins

in the extracellular fluid

◦Cell-mediated response Involves cytotoxic T cells that destroy

infected body cells, cancer cells and transplanted tissues

Relies upon Helper T cells to activate B cells and cytotoxic T cells

Acquired ImmunityOnly found in vertebratesT cells and B cells

◦Types of WBCs called lymphocytes◦Originate from stem cells in the bone marrow◦Some lymphocytes migrate from the marrow

to the thymus These mature into T cells

◦Some lymphocytes remain in the marrow These develop into B cells

◦Other lymphocytes stay in the blood and become the natural killer cells of innate immunity

Acquired ImmunityAntigens are substances that prompt a

response from a B or T cellAntigen receptor proteins allow B and T

cells to bind to antigens◦Specific enough to bind to just one part of

one molecule from a particular pathogen◦Millions of antigen receptors (AR) are

produced, but all AR’s are identical on each B and T cell

◦Up to 100,000 AR’s on the surface of each B and T cell!

◦See Fig. 43.9, page 935

Antigen SpecificsUsually foreignLarge molecules

◦Proteins or polysaccharidesProtrude from the surface of foreign cells or

virusesSome, such as bacterial toxins, are released

into the extracellular fluidSmall, accessible portion that binds to an

AR is called an epitope or antigenic determinant◦Each antigen has several different epitopes, each

binding a receptor with a different specificity

B Cell and Antibody-Antigen RecognitionEach B cell AR is a Y-shaped molecule

of 4 polypeptide chains◦Two identical heavy chains◦Two identical light chains◦Fig. 43.9, page 935

Light and heavy chains have a constant region where amino acid sequences don’t vary much and a variable region on which the amino acid sequence varies extensively from one B cell to another

Formation of AntibodiesWhen a B cell AR binds to an antigen, that will elicit

B cell activation eventually leading to the formation of cells that secrete a soluble form of the receptor◦ The secreted protein is an antibody or immunoglobulin

(Ig)Antibodies are Y-shaped like the B cell AR’s

◦ But are secreted rather than membrane-bound◦ Antibodies are the proteins that defend against

pathogens◦ Differences in amino acid sequences of variable regions

on the B cell AR’s allow highly specific bindingB cell AR’s and antibodies bind to intact antigens in

the blood and lymphFig. 43.10, page 936

T Cell Antigen RecognitionT cell AR’s are two different polypeptide

chains, an α chain and a β chain, linked by a disulfide bridge (fig. 43.11, page 936)

Outer tips of each chain consist of the variable region and are where the antigen binds

Remainder of the molecule is the constant region

Bind to fragments of antigens that are presented on the surface of host cells◦ The host protein that displays the antigen

fragment on the cell surface is the MHC (major histocompatibility complex) molecule

Recognition of Protein Antigens by T CellsBegins when a pathogen or part of a pathogen

either infects of is taken in by a host cell (Fig. 43.12, page 937)

Enzymes in the host cell break the antigen into smaller peptides called antigen fragments◦ These bind to MHC molecules inside the cell◦ MHC molecule with the bound antigen fragment move to

the cell surface resulting in antigen presentation This advertises that the host cell contains a foreign substance

If the cell displaying an antigen fragment encounters a T cell that is the right match, the AR on the T cell will bind to the antigen fragment and the MHC molecule◦ This binding is necessary for a T cell to participate in an

adaptive immune response

Acquired ImmunityActive immunity: acquired

when body produces antibodies and develops immunological memory from either exposure to actual pathogen OR from immunization/vaccinization◦Vaccine can be:

1) inactive toxic 2) killed/weakened microbe 3) portion of microbe 3) genes for microbial proteins

Passive ImmunityPassive immunity: temporary

immunity provided by antibodies◦Supplied through:

Placenta to fetus Milk to nursing infant Antibody injection

Tissue TransplantLimited by immune system’s ability to

distinguish self from nonselfImmune system responds negatively

to chemical markers (unlike itself) during blood transfusions (and tissue transplantation)

Mother and fetus: Rh factor◦Rh: protein, RBCs antigen◦If fetal blood is different from mother,

fetal blood can leak across placenta (creating immunological response from mother)

Tissue Transplantation

Organ and Tissue Transplants◦May be rejected b/c the foreign MHC

molecules are antigenic◦Triggers immune response◦Use closely related donors and

immune system suppressor drugs to minimize risk of rejection

Immune System DiseasesAllergies

◦Hypersensitivity to certain environmental antigens (allergens)

◦Releases histamines – creating inflammatory response that may include: Sneezing Runny nose Difficulty breathing

◦Antihistamine drugs – those that combat these symptoms by blocking histamine receptors

◦Ex: Asthma, eczema (dry skin), environmental allergies (dust, dust mites, grass)

Immune System DiseasesAutoimmune Disease

◦Ex: Lupus, rheumatoid arthritis, insulin-dependent diabetes mellitus, multiple sclerosis

◦May be caused by failure in regulation of self-reactive lymphocytes

◦Causes immune system to turn against itself◦Ex: Scleroderma, a chronic autoimmune

disease that can lead to inflammation and damage of the skin, joints, and internal organs

◦Ex: Ankylosing spondylitis, a disease that involves inflammation of the spine and joints, causing stiffness and pain

Immune System DiseasesImmunodeficiency diseases

◦Ex: AIDS (caused by HIV), cancer, Hodgkin’s disease, stress

◦Suppress the immune system◦Become highly susceptible to

opportunitistic infections (like pneumonia, flu, etc)

◦Ex: DiGeorge syndrome (thymic dysplasia), a birth defect in which kids are born without a thymus gland

◦Ex: Chediak-Higashi syndrome and chronic granulomatous disease both involve the inability of the neutrophils to function normally

Exclusion StatementsMemorization of the structures of

specific antibodies is beyond the scope of the course and the AP Exam.